Toxicity analysis
The primary objective behind the failure of the majority of compounds in drug discovery process is the issues related to pharmacokinetics and toxicity. In the present investigation, these issues were addressed with the help of OSIRIS property explorer program. The pharmacokinetic property of a lead compound can be investigated by utilizing the parameters such as clogP and logS. The result is shown in Table 3. clogP is an entrenched measure of the compound’s hydrophilicity. The high log P values may cause poor retention because of the compound’s low hydrophilicity. It has been demonstrated that for compounds to have a reasonable probability of being well absorbed, their log P value must not be greater than 5.0. It is clear from the table that log P values of all the 60 compounds found to be in the acceptable criteria.
Table 3 Toxicity risks and physicochemical properties of crizotinib and virtual compounds predicted by OSIRIS property explorer
S. no Compound ID Mutagenic Tumorigenic Reproductive effective cLogP Solubility Drug likeness Drug score
1 Crizotinib No No No 3.54 −5.26 3.12 0.52
2 CID: 11597571 No No No 3.54 −5.26 3.12 0.52
3 CID: 11626560 No No No 3.54 −5.26 3.12 0.52
4 CID: 53234260 No No No 3.54 −5.26 3.12 0.52
5 CID: 53234326 No No No 3.54 −5.26 3.12 0.52
6 CID: 56671814 No No No 3.54 −5.26 3.12 0.52
7 CID: 60197531 No No No 3.54 −5.26 3.12 0.52
8 CID: 60197626 No No No 3.54 −5.26 3.12 0.52
9 CID: 60198523 No No No 3.54 −5.26 3.12 0.52
10 CID: 60198524 No No No 3.54 −5.26 3.12 0.52
11 CID: 60198525 No No No 3.54 −5.26 3.12 0.52
12 CID: 60199015 No No No 3.54 −5.26 3.12 0.52
13 CID: 60199016 No No No 3.54 −5.26 3.12 0.52
14 CID: 60199073 No No No 3.54 −5.26 3.12 0.52
15 CID: 60199075 No No No 3.54 −5.26 3.12 0.52
16 CID: 60199076 No No No 3.54 −5.26 3.12 0.52
17 CID: 60199077 No No No 3.54 −5.26 3.12 0.52
18 CID: 62705017 No No No 3.54 −5.26 3.12 0.52
19 CID: 68625002 No No No 3.78 −5.69 3.68 0.46
20 CID: 54613769 No No No 3.54 −5.26 3.22 0.53
21 CID: 11662380 No No Yes 3.54 −5.26 2.78 0.42
22 CID: 11626823 No No No 3.29 −5.78 3.45 0.48
23 CID: 58659191 No Yes No 3.64 −5.58 3.17 0.29
24 CID: 44560358 No No No 3.25 −5.19 2.42 0.54
25 CID: 71239831 No No No 4.19 −5.96 1.79 0.38
26 CID: 71239833 No No No 4.19 −5.96 1.45 0.37
27 CID: 71240010 No No No 4.19 −5.96 1.79 0.38
28 CID: 71240011 No No No 4.19 −5.96 1.79 0.38
29 CID: 11496366 No No No 3.79 −4.90 7.62 0.54
30 CID: 11562021 No No No 4.2 −5.22 7.51 0.48
31 CID: 11626824 No No No 3.79 −4.90 7.62 0.54
32 CID: 11598102 No No No 3.89 −6.11 2.11 0.41
33 CID: 11641497 No No No 2.38 −4.53 4.34 0.49
34 CID: 11690598 No No No 3.03 −4.84 3.12 0.6
35 CID: 68563708 No No No 3.03 −4.84 3.12 0.6
36 CID: 11562217 No No No 3.44 −5.35 2.82 0.29
37 CID: 11612136 No No No 3.68 −5.4 −0.93 0.33
38 CID: 58659130 No No No 3.03 −4.84 3.22 0.60
39 CID: 11625675 No No No 3.75 −5.39 2.56 0.53
40 CID: 67084493 No No No 4.04 −6.15 1.21 0.37
41 CID: 11676204 No No No 2.28 −4.96 3.76 0.62
42 CID: 11684380 No No No 3.55 −5.42 7.62 0.54
43 CID: 58659192 No Yes No 4 −6.42 2.17 0.22
44 CID: 59599446 No No No 2.47 −5.33 4.07 0.53
45 CID: 11503318 No No No 3.01 −5.73 0.63 0.42
46 CID: 11510387 No No No 3.30 −6.39 3.37 0.47
47 CID: 11568619 No No No 3.01 −5.73 0.63 0.42
48 CID: 11575401 No No No 2.85 −4.72 3.34 0.63
49 CID: 11647760 No No No 3.20 −4.99 3.81 0.58
50 CID: 58659136 No No No 3.20 −4.99 3.81 0.48
51 CID: 58659189 Yes No No 3.78 −5.29 4.46 0.31
52 CID: 72986690 No No No 3.01 −5.73 0.63 0.42
53 CID: 11676140 No No No 4.16 −5.75 1.66 0.44
54 CID: 58659141 No No No 3.44 −5.91 −0.32 0.33
55 CID: 11705849 No No No 4.15 −5.74 2.96 0.42
56 CID: 11719356 No No No 3.63 −4.96 2.31 0.53
57 CID: 11647759 No No No 2.61 −5.24 3.45 0.57
58 CID: 21110753 No No No 2.52 −4.67 3.67 0.59
59 CID: 21110757 No No No 3.00 −5.47 2.35 0.56
60 CID: 73386634 No No No 3.00 −5.47 2.35 0.56
61 CID: 11647795 No No No 3.34 −5.13 0.85 0.48
Drug solubility normally affects the absorption and distribution characteristics of a compound. Infact, insufficient solubility of drug can lead to poor absorption (Lipinski et al. 1997). Our evaluated log S worth is a unit stripped logarithm (base 10) of a compound’s dissolvability measured in mol/liter. There are more than 80 % of the drugs available in the market have an (expected) log S value greater than −4. It is clear from the Table 3 that the solubility of the 60 lead compounds was found in the comparable zone with that of standard drugs to fulfill the requirements of solubility and this could be regarded as a candidate drug for oral absorption.